Search

Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG

1359 FIRST SVR DATA WITH THE NUCLEOSIDE ANALOGUE POLYMERASE INHIBITOR MERICITABINE (RG7128) COMBINED WITH PEGINTERFERON/RIBAVIRIN IN TREATMENT-NAIVE HCV G1/4 PATIENTS: INTERIM ANALYSIS FROM THE JUMP-C TRIAL P. Pockros, D. Jensen, N. Tsai, R.M. Taylor, A. Ramji, C. Cooper, R. Dickson, A. Tice, S. Stancic, D. Ipe, J.A. Thommes, J.M. Vierling. Scripps Clinic Research Center, La Jolla, CA, Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, Hawaii Medical Center, Honolulu, HI, The University of Kansas Hospital Medical Center, Kansas City, KS, USA; Division of Gastroenterology, University of British Columbia, Vancouver, BC, The Ottawa Hospital, Ottowa, ON, Canada; Dartmouth-Hitchcock Medical Center, Lebanon, NH, Infections Limited Hawaii, Honolulu, HI, Roche, Nutley, NJ, Genentech, South San Francisco, CA, Baylor College of Medicine, Houston, TX, USA E-mail: pockros.paul@scrippshealth.org Introduction: Mericitabine (RG7128, MCB) is a potent, selective nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase with activity across all HCV genotypes. MCB has demonstrated a high barrier to resistance without treatmentemergent resistance observed to date. Methods: JUMP-C is an ongoing randomised, double-blind, placebocontrolled phase 2b study in treatment naive patients infected with HCV G1/4. The trial objective was to compare a response guided therapy regimen of MCB plus peginterferon alfa-2a/ribavirin (P/R) with P/R alone. Patients randomised to arm A achieving an extended RVR (eRVR; HCVRNA

E.J. Lawitz1, T.D. Boyer2, G.T. Everson3, I.M. Jacobson4, W. Lee5, J.G. McHutchison6, P.J. Pockros7, M.L. Shiffman8, J.M. Vierling9, S. Cruickshank10, B. Armstrong11, T.C. Rodell12, D. Apelian12 1Alamo Medical Research, San Antonio, TX, 2University of Arizona, Tucson, AZ, 3Department of Medicine, University of Colorado Denver, Aurora, CO, 4Department of Medicine, Weill Cornell Medical College, New York, NY, 5Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 6Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, 7The Scripps Clinical Research Center, La Jolla, CA, 8Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, 9Department of Medicine and Surgery, Baylor College of Medicine, Houston, TX, 10Cruickshank and Associates, Santa Barbara, CA, 11QST Consultations, Allendale, MI, 12GlobeImmune, Inc., Louisville, CO, USA

13.6±1.8 g/dL [8.8–17.5], respectively. After 12W, a complete early virological response was obtained in 34 (83%) boceprevir patients and in 35 (61%) telaprevir patients (p = 0.026). Among 17 boceprevir and 16 telaprevir patients, 14 (82%) and 7 (43%) achieved an end of treatment response (EOT) with an undetetectable viral load, respectively (p = 0.032). Among 9 boceprevir and 5 telaprevir patients, 6 and 1 achieved SVR12, respectively. Among 6 patients in the boceprevir group, 3 achieved SVR24. In the telaprevir group, 29 patients discontinued therapy (serious adverse events, n = 13; virological breakthrough, n = 6; non-response, n = 9). In the boceprevir group, 14 patients discontinued therapy (serious adverse events, n = 5; virological breakthrough, n = 2; non-response, n = 4; retransplantation, n = 1). Four patients died in a context of infectious disorders: boceprevir, n = 2 (W20/W24); telaprevir, n = 2 (W2/W9). The most common side effect was anemia in 85% of patients: 95% and 96% in boceprevir and telaprevir groups received erythropoietin alone or combined with ribavirin dose reduction. Conclusion: In liver transplanted patients, EOT rate was 82% and 38% with boceprevir and telaprevir, respectively. Among the overall population, 44% of patients discontinued therapy because of treatment failure or occurrence of serious adverse events.

1181 PHARMACOGENOMIC ANALYSIS REVEALS IMPROVED VIROLOGIC RESPONSE IN ALL IL-28B GENOTYPES IN NAIVE GENOTYPE 1 CHRONIC HCV PATIENTS TREATED WITH GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN J.G. McHutchison, A.J. Thompson, I.M. Jacobson, T.D. Boyer, E.R. Schiff, G.T. Everson, J.M. Vierling, M.L. Shiffman, R.S. Brown, A.M. Di Bisceglie, S.C. Gordon, W.M. Lee, Z. Guo, T.H. King, B. Armstrong, T.C. Rodell, D. Apelian. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, Center for Liver Diseases, University of Miami School of Medicine, Miami, FL, Department of Medicine, University of Colorado Denver, Aurora, CO, Department of Medicine and Surgery, Baylor College of Medicine, St. Luke’s Episcopal Hospital, Houston, TX, Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, Columbia University College of Physicians & Surgeons, New York, NY, Saint Louis University, St. Louis, MO, Henry Ford Hospital, Detroit, MI, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, GlobeImmune, Inc., Louisville, CO, QST Consultations, LTD, Allendale, MI, USA E-mail: mchut001@mc.duke.edu

276 WEEK 4 HCVRNA IS THE OPTIMAL PREDICTOR OF SVR IN BOTH HIV POSITIVE AND NEGATIVE SUBJECTS WITHIN THE AUSTRALIAN TRIAL IN ACUTE HCV G.V. Matthews, J. Grebely, M. Hellard, B. Yeung, P. Marks, W. Rawlinson, J. Kaldor, G.J. Dore, ATAHC Study Group. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales, Sydney, NSW, Burnet Institute, Melbourne, VIC, Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, NSW, Australia E-mail: gmatthews@nchecr.unsw.edu.au